epoetin-alfa and Neutropenia

To review the hematologic adverse effects of hepatitis C virus (HCV) therapy and adjuvant treatment with epoetin alfa and granulocyte colony-stimulating factor (ie, filgrastim).. Medical literature indexed in MEDLINE (1966-January 2007) and EMBASE (1980-January 2007) was searched, and published conference abstracts were reviewed.. Peer-reviewed articles and relevant conference abstracts regarding the use of epoetin alfa and granulocyte colony-stimulating factor were reviewed.. Ribavirin induces a dose-dependent hemolytic anemia. Studies using epoetin alfa 40 000 units subcutaneously once weekly have demonstrated efficacy in maintaining hemoglobin, ribavirin dose, and quality of life scores, but clear benefit shown with sustained virologic response (SVR) is lacking. The hemoglobin threshold for initiation of epoetin alfa used in studies may not adequately reflect values used in clinical practice. Treatment-related neutropenia is caused primarily by interferon or peginterferon. Few studies have investigated the impact of granulocyte or granulocyte-macrophage colony-stimulating factor derivatives on neutropenia. Results of dose maintenance evaluation vary, and studies reporting data on SVR showed no effect from growth factor therapy. The frequency of bacterial infections was not reported.. The role and benefit of hematopoietic growth factors in HCV therapy have not been conclusively determined to date. However, the possibility of a benefit to individual patients seen on an outpatient basis remains, and an individualized treatment approach is recommended.

Topics: Anemia; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Hepatitis C; Humans; Interferons; MEDLINE; Neutropenia; Recombinant Proteins; Ribavirin

Hematologic side effects (anemia, neutropenia, and thrombocytopenia) of combination therapy with pegylated (PEG)-interferon alfa and ribavirin are commonly encountered during antiviral therapy for chronic hepatitis C (HCV). An important consequence of these side effects is dose modification of PEG-interferon alfa, ribavirin, or both. Dose modification (including discontinuation) diminishes the efficacy of optimal treatment regimen for HCV and may have a negative impact on sustained virologic response. Additionally, fatigue associated with anemia may impair patients' quality of life. The clinical implications of neutropenia or thrombocytopenia are less clear than for anemia; nevertheless, severe infection and bleeding are uncommon. Dose adjustments effectively treat these hematologic side effects, but the resulting suboptimal dosing and potential impact on virologic response are major concerns. Recent attempts to maximize adherence to the optimal treatment regimen have used hematopoietic growth factors rather than dose adjustment to treat side effects. Research on growth factor support has focused on anemia and neutropenia. Epoetin alfa and darbepoetin alfa are erythropoietic growth factors that effectively increase hemoglobin while maintaining the optimal ribavirin dose and improving patients' quality of life. Preliminary work suggests that filgrastim, granulocyte colony stimulating factors, may be an effective treatment of interferon-induced neutropenia. Although this early work shows tremendous promise for managing hematologic side effects of combination therapy for HCV, and potentially enhancing adherence, further research is needed to clarify the efficacy, safety, and cost-effectiveness of growth factors in the management of patients with chronic HCV.

Topics: Anemia, Hypochromic; Antiviral Agents; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Granulocyte Colony-Stimulating Factor; Growth Substances; Hematinics; Hematologic Diseases; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Thrombocytopenia

Consensus guidelines are in place for treating chronic hepatitis C virus infection. This article highlights some of the hematologic complications of hepatitis C therapy. Management options are presented.

Topics: Anemia; Antiviral Agents; Bone Marrow; Epoetin Alfa; Erythropoietin; Hematologic Diseases; Hepatitis C, Chronic; Humans; Interferon Type I; Neutropenia; Recombinant Proteins; Ribavirin; Thrombocytopenia

Hematologic abnormalities such as anemia, neutropenia, and thrombocytopenia are common during combination therapy with pegylated (or standard) interferon and ribavirin for chronic hepatitis C. Ribavirin-induced hemolytic anemia is a common cause of dose reduction or discontinuation. Bone marrow suppression also contributes to the anemia and is the predominant mechanism for interferon-induced neutropenia and thrombocytopenia. Although dose reduction or discontinuation of combination therapy can reverse these abnormalities, they may reduce virologic response. Hematopoietic growth factors may provide a useful alternative for managing these hematologic side effects without reducing the optimal dose of the combination antiviral regimen. Treatment of anemia also may improve patients' health-related quality of life and their adherence to combination antiviral therapy. The impact of growth factors on sustained virologic response and their cost-effectiveness in patients with chronic hepatitis C need further assessment.

Topics: Anemia; Antiviral Agents; Clinical Trials as Topic; Darbepoetin alfa; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hepatitis C, Chronic; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Interleukin-11; Neutropenia; Patient Compliance; Polyethylene Glycols; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Ribavirin; Thrombocytopenia

Myelosuppression associated with cancer chemotherapy may lead to neutropenia, anemia, or both, resulting in an increased risk for infection, fatigue, diminished quality of life, and reduced survival. In addition, neutropenia specifically has been shown to result in dose reductions, treatment delays, or both in subsequent chemotherapy cycles. Hematopoietic growth factors have been used effectively as supportive therapy to reduce chemotherapy-associated neutropenia and anemia. New preparations have the potential to improve treatment outcome dramatically. Results from recently reported studies indicate that patients at risk for neutropenia can be safely and effectively treated with pegfilgrastim once per chemotherapy cycle, and that those with anemia can be managed with weekly or biweekly darbepoetin alfa therapy. These new treatments have the potential to reduce the morbidity and mortality associated with opportunistic infections, decrease the requirement for potentially dangerous blood transfusions, and improve the quality of life for patients undergoing cancer chemotherapy. The longer dosing intervals offered by these new preparations may decrease healthcare expenses and enhance patient adherence.

Topics: Anemia; Antineoplastic Agents; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Neutropenia; Polyethylene Glycols; Recombinant Proteins

Erythropoiesis-stimulating agents (ESAs) are the standard-of-care treatment for anaemia in most patients with lower-risk myelodysplastic syndromes but responses are limited and transient. Luspatercept promotes late-stage erythroid maturation and has shown durable clinical efficacy in patients with lower-risk myelodysplastic syndromes. In this study, we report the results of a prespecified interim analysis of luspatercept versus epoetin alfa for the treatment of anaemia due to lower-risk myelodysplastic syndromes in the phase 3 COMMANDS trial.. The phase 3, open-label, randomised controlled COMMANDS trial is being conducted at 142 sites in 26 countries. Eligible patients were aged 18 years or older, had a diagnosis of myelodysplastic syndromes of very low risk, low risk, or intermediate risk (per the Revised International Prognostic Scoring System), were ESA-naive, and required red blood cell transfusions (2-6 packed red blood cell units per 8 weeks for ≥8 weeks immediately before randomisation). Integrated response technology was used to randomly assign patients (1:1, block size 4) to luspatercept or epoetin alfa, stratified by baseline red blood cell transfusion burden (<4 units per 8 weeks vs ≥4 units per 8 weeks), endogenous serum erythropoietin concentration (≤200 U/L vs >200 to <500 U/L), and ring sideroblast status (positive vs negative). Luspatercept was administered subcutaneously once every 3 weeks starting at 1·0 mg/kg body weight with possible titration up to 1·75 mg/kg. Epoetin alfa was administered subcutaneously once a week starting at 450 IU/kg body weight with possible titration up to 1050 IU/kg (maximum permitted total dose of 80 000 IU). The primary endpoint was red blood cell transfusion independence for at least 12 weeks with a concurrent mean haemoglobin increase of at least 1·5 g/dL (weeks 1-24), assessed in the intention-to-treat population. Safety was assessed in patients who received at least one dose of study treatment. The COMMANDS trial was registered with ClinicalTrials.gov, NCT03682536 (active, not recruiting).. Between Jan 2, 2019 and Aug 31, 2022, 356 patients were randomly assigned to receive luspatercept (178 patients) or epoetin alfa (178 patients), comprising 198 (56%) men and 158 (44%) women (median age 74 years [IQR 69-80]). The interim efficacy analysis was done for 301 patients (147 in the luspatercept group and 154 in the epoetin alfa group) who completed 24 weeks of treatment or discontinued earlier. 86 (59%) of 147 patients in the luspatercept group and 48 (31%) of 154 patients in the epoetin alfa group reached the primary endpoint (common risk difference on response rate 26·6; 95% CI 15·8-37·4; p<0·0001). Median treatment exposure was longer for patients receiving luspatercept (42 weeks [IQR 20-73]) versus epoetin alfa (27 weeks [19-55]). The most frequently reported grade 3 or 4 treatment-emergent adverse events with luspatercept (≥3% patients) were hypertension, anaemia, dyspnoea, neutropenia, thrombocytopenia, pneumonia, COVID-19, myelodysplastic syndromes, and syncope; and with epoetin alfa were anaemia, pneumonia, neutropenia, hypertension, iron overload, COVID-19 pneumonia, and myelodysplastic syndromes. The most common suspected treatment-related adverse events in the luspatercept group (≥3% patients, with the most common event occurring in 5% patients) were fatigue, asthenia, nausea, dyspnoea, hypertension, and headache; and none (≥3% patients) in the epoetin alfa group. One death after diagnosis of acute myeloid leukaemia was considered to be related to luspatercept treatment (44 days on treatment).. In this interim analysis, luspatercept improved the rate at which red blood cell transfusion independence and increased haemoglobin were achieved compared with epoetin alfa in ESA-naive patients with lower-risk myelodysplastic syndromes. Long-term follow-up and additional data will be needed to confirm these results and further refine findings in other subgroups of patients with lower-risk myelodysplastic syndromes, including non-mutated SF3B1 or ring sideroblast-negative subgroups.. Celgene and Acceleron Pharma.

Topics: Aged; Anemia; Body Weight; COVID-19; Dyspnea; Epoetin Alfa; Erythropoiesis; Female; Hematinics; Hemoglobins; Humans; Hypertension; Male; Myelodysplastic Syndromes; Neutropenia

We performed a phase I study of two fixed dosing schemes of cisplatin, a DNA cross-linker, with intravenous escalating topotecan, a DNA-topoisomerase I inhibitor.. 40 patients with advanced solid tumors received intravenous cisplatin at a fixed dose of either 25 mg/m2 (schedule A) or 20 mg/m2 (schedule B) daily for 3 days with standard hydration. Topotecan escalation proceeded in 0.75, 0.90, 1.0, 1.15 mg/m2 cohorts in schedule A and 1.0, 1.1, 1.2, 1.3 mg/m2 cohorts in schedule B, administered intravenously at the end of cisplatin infusion daily for 3 days, repeated every 3 weeks. Dose-limiting toxicity (DLT) consisted of protracted grade IV neutropenia, febrile neutropenia, grade IV thrombocytopenia and any grade III/IV non-hematological toxicity. Epoetin and granulocyte colony-stimulating factor support was allowed on severe myeloablation. Endpoints were the identification of maximal tolerated dose (MTD), DLT and other toxicity.. The MTD was reached in cohort 25/1.15 mg/m2 in schedule A and 20/1.2 mg/m2 in schedule B. All DLT seen consisted of three episodes of febrile neutropenia and two of grade IV thrombocytopenia in schedule A, with three episodes of febrile neutropenia and one of protracted neutropenia in schedule B. Myelosuppression was substantial in all cohorts despite granulocyte colony-stimulating factor and epoetin support, peaked on the third week of treatment and resulted in administration of chemotherapy at a median of every 4 weeks. Non-hematologic toxicity was mild. The response rate was 51% with seven complete responses occurring in patients with ovarian cancer, small cell and non-small cell lung cancer and cancer of unknown primary. The recommended dose was 20/ 1.1 mg/m2 for cisplatin and topotecan on schedule B, as the number of responses and administered topotecan dose were higher in schedule B recommended dose with lower cisplatin dose, minimizing problems of nephrotoxicity and vomiting.. The schedule B daily cisplatin-topotecan x 3 combination with secondary cytokine support is associated with promising activity and schedule convenience. However, substantial myelosuppression undermines its applicability in the palliative setting, stressing the need for less toxic regimens.

Topics: Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Infusions, Intravenous; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Neutropenia; Recombinant Proteins; Topotecan

This randomized, placebo-controlled trial was designed to assess the efficacy and safety of therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (epoetin alfa) in anemic, neutropenic patients with myelodysplastic syndrome. Sixty-six patients were enrolled according to the following French-American-British classification: refractory anemia (20), refractory anemia with excess blasts (35), refractory anemia with ringed sideroblasts (9), and refractory anemia with excess blasts in transformation (2). Patients were stratified by their serum erythropoietin levels (less than or equal to 500 mU/mL, n = 37; greater than 500 mU/mL, n = 29) and randomized, in a 2:1 ratio, to either GM-CSF (0.3-5.0 microg/kg.d) + epoetin alfa (150 IU/kg 3 times/wk) or GM-CSF (0.3-5.0 microg/kg.d) + placebo (3 times/wk). The mean neutrophil count rose from 948 to 3831 during treatment with GM-CSF +/- epoetin alfa. Hemoglobin response (increase greater than or equal to 2 g/dL, unrelated to transfusion) occurred in 4 of 45 (9%) patients in the GM-CSF + epoetin alfa group compared with 1 of 21 (5%) patients with GM-CSF + placebo group (P = NS). Percentages of patients in the epoetin alfa and the placebo groups requiring transfusions of red blood cells were 60% and 92%, respectively, for the low-endogenous erythropoietin patients and 95% and 89% for the high-endogenous erythropoietin patients (P = NS). Similarly, the average numbers of units of red blood cells transfused during the 12-week study in the epoetin alfa and the placebo groups were 5.9 and 9.5, respectively, in the low-endogenous erythropoietin patients and 9.7 and 8.6 in the high-endogenous erythropoietin patients (P = NS). GM-CSF +/- epoetin alfa had no effect on mean platelet count. Treatment was well tolerated in most patients, though 10 withdrew from the study for reasons related predominantly to GM-CSF toxicity. (Blood. 2000;95:1175-1179)

Topics: Anemia; Blood Transfusion; Double-Blind Method; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Female; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Male; Middle Aged; Myelodysplastic Syndromes; Neutropenia; Placebos; Recombinant Proteins

Inpatient costs associated with different erythropoietic-stimulating therapy regimens have not been compared in an oncology setting.. To conduct a cost analysis of different regimens of epoetin alfa (EPO) and darbepoetin alfa (DARB) in an inpatient oncology setting.. A retrospective evaluation of oncology diagnosis-related group discharges during 2003, in 30 community hospitals, identified EPO treatment patterns. Wholesale acquisition costs were determined for patients who received EPO 40,000 units or more once weekly. Potential differences in costs were calculated using conversion ratios for an equivalent EPO dose 3 times weekly or DARB dose once weekly (EPO:DARB ratio 260:1, approximating DARB 150 microg once weekly). A sensitivity analysis was performed using an EPO:DARB ratio of 400:1, approximating DARB 100 microg once weekly (1.5 microg/kg).. Among the 1410 EPO doses administered (n = 677 pts.), a dose of 40,000 units or more was used 44% of the time (n = 311 pts.), with dosing initiated on average 5.6 days after admission. For these 311 evaluable patients, switching from EPO 40,000 units once weekly to EPO 10,000 units 3 times weekly reduced per-patient and total drug acquisition costs by approximately 50% (704 US dollars vs 359 US dollars and 218,938 US dollars vs 111,615 US dollars, respectively). Relative to EPO once weekly, switching patients to DARB resulted in increased drug acquisition costs at the 260:1 conversion and lower costs at the 400:1 conversion. However, EPO 3 times weekly remained the least costly option by 44-63%. The cost-savings realized with EPO 10,000 units 3 times weekly increased with longer duration of hospitalization.. In an inpatient setting, use of EPO 10,000 units 3 times weekly may minimize expenditures associated with treatment of cancer-related anemia using erythropoietic-stimulating therapies.

Topics: Algorithms; Costs and Cost Analysis; Darbepoetin alfa; Dose-Response Relationship, Drug; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Neutropenia; Recombinant Proteins

Topics: Anemia; Antibodies, Monoclonal; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cyclophosphamide; Doxorubicin; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Humans; Lymphoma, Large B-Cell, Diffuse; Middle Aged; Neutropenia; Polyethylene Glycols; Positron-Emission Tomography; Prednisone; Recombinant Proteins; Rituximab; Stomach Neoplasms; Vincristine

Current therapy for the treatment of hepatitis C virus (HCV) infection is standard interferon (IFN) or pegylated interferon (PEG-IFN) in combination with ribavirin (RBV). Hematologic side effects (neutropenia, thrombocytopenia, anemia) are a major reason for dose reduction of anti-HCV therapy. Because treatment adherence and maintenance of IFN or PEG-IFN and RBV doses have been shown to be important in achieving a sustained virologic response, appropriate management of hematologic side effects might play a substantial role in optimizing treatment outcomes. Neutropenia and thrombocytopenia are usually managed by IFN or PEG-IFN dose reduction; the role of hematopoietic growth factors to ameliorate these side effects needs further evaluation, but some studies suggest granulocyte colony-stimulating factor (G-CSF) may be useful in the management of IFN/PEG-IFN-associated neutropenia. Anemia is primarily due to RBV-induced hemolytic anemia, but IFN/PEG-IFN also suppresses bone marrow erythroid precursors. Treatment-induced anemia has usually been managed by RBV dose reduction or discontinuation. However, recent studies suggest that epoetin alfa can increase hemoglobin levels and facilitate maintenance of RBV dosage in patients with chronic hepatitis C who became anemic during standard combination therapy. Results of a randomized, randomized, double-blind, placebo-controlled trial suggest that epoetin alfa therapy can maintain RBV dosage, increase hemoglobin levels, and improve quality of life in this population. In patients who have chronic hepatitis C who experience hematologic toxicities during standard therapy, the use of hematopoietic growth factors such as epoetin alfa might have the potential to improve treatment adherence rates and allow optimal doses of IFN or PEG-IFN and RBV to be maintained, thereby leading to improved treatment outcomes.

Topics: Anemia; Antiviral Agents; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Hematinics; Hepatitis C; Humans; Interferon alpha-2; Interferon-alpha; Interferons; Neutropenia; Polyethylene Glycols; Recombinant Proteins; Ribavirin; Thrombocytopenia

Strategies for managing antineoplastic therapy-associated hematopoietic toxicity (thrombocytopenia, neutropenia, and anemia) are discussed. Hemorrhage secondary to decreases in platelets is the major risk posed by chemotherapy-induced thrombocytopenia. Patients with < 20,000 platelets per microliter are at increased risk of bleeding, particularly if they have a history of bleeding associated with this condition. The risks of infection and complications are related to both the severity and duration of neutropenia. The rate of febrile neutropenia with most antineoplastic regimens is < 40%, and routine use of cytokine therapy is probably not cost-effective. The frequency of cancer-related anemia is dependent on the type, stage, and duration of disease. Chemotherapy-induced anemia is affected by the types of agents used, the schedule of drug administration, and the intensity of the regimen. Fatigue is the most common symptom of anemia, being reported by 80-100% of patients undergoing chemotherapy. Although fatigue is a major factor in patients' quality of life, it has often not been treated systematically and aggressively. Anemia used to be treated with transfusions, but therapy with epoetin alfa is showing promise as an alternative. The introduction of epoetin alfa has led to more aggressive treatment. Chemotherapy-induced hematopoietic toxicity is a multifactorial challenge that affects the treatment of oncology patients.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Fatigue; Hematinics; Humans; Neutropenia; Practice Guidelines as Topic; Recombinant Proteins; Severity of Illness Index; Thrombocytopenia

To define the incidence, course, and etiology of hematologic abnormalities in children on tacrolimus-based immunosuppression, we reviewed records of 106 transplant patients (70 heart, 16 heart and lung, 20 double lung), 0-21 yr of age, who were transplanted at the Children's Hospital of Pittsburgh from 1989 to 1997. Fifty-four of the 106 patients (51%) developed 65 abnormal hematologic episodes (32 anemia, nine neutropenia, nine thrombocytopenia, 15 simultaneous anemia and neutropenia with or without thrombocytopenia). Common etiologies included: infections, post-transplant lymphoproliferative disease, and medications. Eleven episodes (seven anemia, one neutropenia, and three simultaneous anemia and neutropenia) had unclear etiologies and process of elimination suggested an association with tacrolimus. Interventions included filgrastim (effective in 15 of 15 patients, with resolution of neutropenia in a median of 5 days) and epoetin alfa (effective in five of 16 patients, including four of four patients with anemia possibly related to tacrolimus). Five patients (two with neutropenia and three with simultaneous neutropenia and anemia) were switched to cyclosporin A (CsA); rapid resolution occurred in four of the five patients, suggesting a possible association of the hematologic abnormalities with tacrolimus. In summary, hematologic abnormalities are common in children on tacrolimus-based immunosuppression. Most of these hematologic abnormalities are caused by common etiologies; however, a sub-population exists where tacrolimus may be the etiologic agent. Anemia and neutropenia respond to treatment with epoetin alfa and filgrastim. After thorough investigation, a trial switch to CsA may be warranted.

Topics: Adolescent; Adult; Anemia; Child; Child, Preschool; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Heart Transplantation; Heart-Lung Transplantation; Hematologic Diseases; Humans; Immunosuppressive Agents; Infant; Lung Transplantation; Male; Neutropenia; Recombinant Proteins; Retrospective Studies; Tacrolimus; Thrombocytopenia